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      Effectiveness of influenza vaccines in adults with chronic liver disease: a systematic review and meta-analysis

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          Patients with liver disease frequently require hospitalisation with infection often the trigger. Influenza vaccination is an effective infection prevention strategy in healthy and elderly but is often perceived less beneficial in patients with liver disease. We investigated whether influenza vaccination triggered serological response and prevented hospitalisation and death in liver disease.


          Systematic review and meta-analysis.

          Data sources

          MEDLINE, EMBASE, PubMed and CENTRAL up to January 2019.

          Eligibility criteria

          Randomised or observational studies of the effects of influenza vaccine in adults with liver disease.

          Data extraction and synthesis

          Two reviewers screened studies, extracted data and assessed risk of bias and quality of evidence. Primary outcomes were all-cause hospitalisation and mortality. Secondary outcomes were cause-specific hospitalisation and mortality, and serological vaccine response. Random-effects meta-analysis was used to estimate pooled effects of vaccination.


          We found 10 041 unique records, 286 were eligible for full-text review and 12 were included. Most patients had viral liver disease. All studies were of very low quality. Liver patients both with and without cirrhosis mounted an antibody response to influenza vaccination, and vaccination was associated with a reduction in risk of hospital admission from 205/1000 to 149/1000 (risk difference −0.06, 95% CI −0.07 to 0.04) in patients with viral liver disease. Vaccinated patients were 27% less likely to be admitted to hospital compared with unvaccinated patients (risk ratio 0.73, 95% CI 0.66 to 0.80). No effect against all-cause or cause-specific mortality or cause-specific hospitalisation was found.


          The low quantity and quality of the evidence means that the protective vaccine effect may be uncertain. Considering the high risk of serious health outcomes from influenza infection in patients with liver disease and the safety and low cost of vaccination, overall, the potential benefits of seasonal vaccination both to patients and the healthcare systems are likely to outweigh the costs and risks associated with vaccination.

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          Most cited references 23

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          The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews

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            Kupffer cell-dependent hepatitis occurs during influenza infection.

            Respiratory infections, including influenza in humans, are often accompanied by a hepatitis that is usually mild and self-limiting. The mechanism of this kind of liver damage is not well understood. In the present study, we show that influenza-associated hepatitis occurs due to the formation of inflammatory foci that include apoptotic hepatocytes, antigen-specific CD8(+) T cells, and Kupffer cells. Serum aminotransaminase levels were elevated, and both the histological and serum enzyme markers of hepatitis were increased in secondary influenza infection, consistent with a primary role for antigen-specific T cells in the pathogenesis. No virus could be detected in the liver, making this a pure example of "collateral damage" of the liver. Notably, removal of the Kupffer cells prevented the hepatitis. Such hepatic collateral damage may be a general consequence of expanding CD8(+) T-cell populations during many extrahepatic viral infections, yielding important implications for liver pathobiology.
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              A systematic review of the evidence on the effectiveness and risks of inactivated influenza vaccines in different target groups.

              To systematically review the evidence regarding the efficacy, effectiveness and risks of the use of inactivated influenza vaccines in children, healthy adults, elderly individuals and individuals with co-morbidities such as diabetes, chronic lung disease, cardiovascular disease, kidney or liver disease and immune suppression. The Cochrane database of systematic reviews was searched for relevant reviews and supplemented with searches of the Cochrane Central Register of Controlled Trials database and Medline. Two reviewers independently assessed review and trial quality and extracted data. The inactivated influenza vaccine has been proven effective in preventing laboratory-confirmed influenza among healthy adults (16-65 years) and children (≥6 years) (GRADE A evidence). However, there is strikingly limited good-quality evidence (all GRADE B, C or not existing) of the effectiveness of influenza vaccination on complications such as pneumonia, hospitalisation and influenza-specific and overall mortality. Inconsistent results are found in studies among children younger than 6 years, individuals with COPD, institutionalised elderly (65 years or older), elderly with co-morbidities and healthcare workers in elderly homes, which can only be explained by bias of unknown origin. The vaccination of pregnant women might be beneficial for their newborns, and vaccination of children might be protective in non-recipients of the vaccine of all ages living in the same community (one RCT, Grade B evidence). Copyright © 2011 Elsevier Ltd. All rights reserved.

                Author and article information

                BMJ Open
                BMJ Open
                BMJ Open
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                6 September 2019
                : 9
                : 9
                [1 ] departmentInstitute of Health Informatics , University College London , London, UK
                [2 ] departmentDivision of Medicine , University College London , London, UK
                [3 ] departmentInstitute of Epidemiology and Health Care , University College London , London, UK
                Author notes
                [Correspondence to ] Suvi Härmälä; suvi.harmala.14@ 123456ucl.ac.uk
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                Funded by: FundRef http://dx.doi.org/10.13039/501100000268, Biotechnology and Biological Sciences Research Council;
                Award ID: BBSRC BB/M009513/1
                Gastroenterology and Hepatology
                Original Research
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